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(R)-2-(4-Phenylbutyl)dihydrobenzofuran derivatives (e.g., 3 and 4) were synthesized as novel melatoninergic ligands with significantly lower vasoconstrictive activity in vitro in the rat tail artery. Binding affinity assays were performed on cloned human MT1 and MT2 receptors stably expressed in NIH3T3 cells.

It is well-known that the properties of iron are affected by impurities. With a small amount of sulfur, a drastic hot ductility drop appears near 1000 K. Boron in Fe-P alloy improves the grain boundary brittleness at room temperature by intrinsic cohesion mechanism and competition mechanism. In the present research, the intrinsic effect of boron on the hot ductility drop of Fe-S alloy has been investigated. High purity Fe-60 mass ppm S alloys doped with boron (0 to 70 mass ppm) were melted in a CaO crucible using a high vacuum induction furnace. It is found, for example, by tensile tests at 973 K that the reduction in area (RA) increases from 20% to 50% by the addition of about 20 mass ppm boron to a high purity Fe-60 mass ppm S alloy. However, by adding more boron, the RA decreases and then becomes constant with boron contents higher than 35 mass ppm. It is observed that excess sulfur and boron precipitates as iron-sulfide and iron-boride uniformly distributed in the matrix. The decrease in RA by adding more than 10 mass ppm boron is caused by the strengthening of the matrix due to the increase in the number of iron-boride particles. It should be emphasized that experimental research using highly purified specimens is significant to clarify the inherent properties of metals.

An ultra-high purity Fe-0.8 mass%C alloy (UHP alloy) was melted in a newly designed ultra-high vacuum induction melting furnace equipped with a copper cold crucible. Reference materials were also prepared, consisting of a high-purity Fe-0.8 mass%C alloy (HP alloy) and a commercial Fe-0.8 mass%C alloy (Com alloy), which were melted in a high vacuum induction melting furnace at research laboratory. The purity of the UHP, HP and Com alloys were approximately 99.998, 99.943 and 99.033 mass %, respectively. The effect of purification on the microstructure was revealed after various heat-treatments applied to the UHP alloy. It was clarified that the microstructure of Fe-0.8 mass%C alloys, especially the morphology of carbide, is strongly affected by purity. In the UHP alloy, lamellar carbide in pearlite easily dissolved, and spheroidized carbide precipitated.

The application of a convergent benzannulation strategy in an efficient synthesis of (-)-ascochlorin is described.

It is shown that intergranular fracture along prior-austenite grain boundaries in a ultrahigh-strength quenched and tempered 4340-type steel is not suppressed by eliminating all segregated embrittling elements. This leaves open the question of how brittle intergranular cracks are nucleated in hydrogen in the absence of such impurities.

Thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) were examined in the acute stage in 51 patients with nontraumatic subarachnoid hemorrhage. TAT and PIC values were correlated with severity at the time of onset and with outcome. In the patients whose TAT levels were 25 ng/ml or more and PIC levels were 3.0 micrograms/ml or more (n = 16), only 25% had a good or fair outcome. In the patients with TAT levels less than 25 ng/ml or PIC levels less than 3.0 micrograms/ml (n = 35), on the other hand, 82.9% had a good or fair outcome. There were no significant differences in TAT and PIC levels between patients who experienced arterial spasm and those who did not. These results indicate that TAT and PIC values may reflect the severity of the brain damage induced by subarachnoid hemorrhage. It is speculated that marked coagulation and fibrinolytic disorders occur in the acute stage of subarachnoid hemorrhage.

This update includes basic patents and patent applications published between July 1992 and June 1994 which may have utility for the treatment of three major groups of sleep disorders, namely, simple insomnia, sleep disorders secondary to anxiety or mood disorders, and sleep disorders stemming from circadian rhythm disruptions. Accordingly, the patents are grouped by their presumed mode of action as non-psychotropic agents, psychotropic agents, and chronobtotic agents. For the purposes of this review, only those patents and applications which specifically describe or claim sleep enhancing or sedative-hypnotic properties are included. Coverage is limited to novel small-molecule, non-peptidergic agents.

Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P -0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 micrograms/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 micrograms x min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.

The present study was designed to determine the predictive factors for the viral response to pegylated interferon-alpha plus ribavirin combination therapy (PEGIFN/RBV) administered after curative treatment for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). The study group was 78 patients treated between January 2005 and January 2009. The sustained viral response (SVR) rate was 25.8% (15/58) in patients infected with HCV-genotype 1 and 55.0% (11/20) in those with genotype 2. Among the 78 patients, 32 (41.0%) could not complete the treatment protocol, and this was because of HCC recurrence in 17 (53%) of them. Multivariate analysis identified partial early viral response (pEVR) as the only independent determinant of SVR [odds ratio (OR) 14.73, P = 0.013] for patients with genotype 1. Multivariate analysis identified male gender (OR 8.72, P = 0.001) and interleukin-28B (IL-28B) genotype (rs8099917) TT (OR 7.93, P = 0.007) as independent predictors of pEVR. Multivariate analysis also identified IL-28B genotype GG+TG (OR 14.1, P = 0.021) and α-fetoprotein30 (OR 5.4, P = 0.031) as independent predictors of null response. Patients with SVR showed a better survival rate than those without SVR (P = 0.034). The second HCC recurrence rate tended to be lower in patients with SVR than in those without SVR (P = 0.054). With regard to the prognosis of patients with SVR, it is desirable to achieve SVR with interferon therapy even when administered after HCC treatment. IL-28B genotype is a potentially useful marker for the response to PEGIFN/RBV therapy administered after curative treatment of HCV-related HCC.

We previously reported that trapidil, a Platelet-derived Growth Factor (PDGF) antagonist, can inhibit the proliferation of PDGF-dependent glioma cells. In the current study, we explored the effect of trapidil on the differentiation of glioma cells by observing the morphological changes in glioma cells in control and trapidil-treated cultures under a phase contrast microscope. Most cells in the control cultures were flat, large, and irregularly shaped. On the other hand, most cells treated with trapidil formed several long cytoplasmic processes and exhibited fibrous morphology. Western blots and immunocytochemical analysis of glial fibrillary acidic protein (GFAP)-stained, trapidil-treated cultures revealed an increase in GFAP content over the control cultures. From these results we propose that trapidil induces the differentiation of glioma cells.

The high affinity IL-5R consists of at least two chains, alpha and beta. IL-5R alpha binds IL-5 with low affinity. IL-5R beta is required to construct the high affinity IL-5R, although IL-5R beta does not bind IL-5 by itself. To characterize the roles of IL-5R alpha and IL-5R beta on the association, dissociation, and internalization of IL-5, we compared the binding kinetics and the internalization of 35S-labeled IL-5 by high affinity IL-5R (dissociation constant approximately 150 pM) bearing T88-M with those by low affinity IL-5R (dissociation constant approximately 30 nM) bearing MOPC104E. We found that association kinetics of IL-5 to either natural receptor were similar. The maximal binding of IL-5 to both high and low affinity IL-5R was rapid (within 10 min). The dissociation of IL-5 from low affinity IL-5R was rapid (t1/2 < 30 min), but that from the high affinity IL-5R was remarkably slower (t1/2 > 120 min). The internalization of IL-5 was observed only in T88-M, but not in MOPC104E, suggesting that IL-5 internalization is mediated via high affinity IL-5R. Association and dissociation kinetics observed in natural cell line were mostly reproduced by the kinetic analysis of reconstituted IL-5R on transfectants with either the IL-5R alpha or the IL-5R alpha and IL-5R beta genes. However, transfectants that expressed IL-5R alpha significantly internalized IL-5, although the level was much lower than observed with IL-5R alpha beta transfectants. These results suggest that IL-5R alpha may be involved in the internalization of IL-5, whereas IL-5R beta is responsible for slowing the dissociation and the efficient internalization of IL-5 by stabilizing the ligand-receptor complex.

The chromosomal location of the human gene for the alpha subunit of interleukin-5 receptor (IL5RA) has been determined. The human IL5RA gene was localized to the short arm of chromosome 3 by Southern blot analysis of DNA from a panel of mouse-human hybrid somatic cell lines. The IL5RA gene has been further localized to human chromosome region 3p24-3p26 by in situ hybridization of a molecularly cloned IL5RA cDNA fragment to metaphase chromosomes. The results suggest that the IL5RA locus is unlinked to other members of the hematopoietic receptor family. Assignment of the IL5RA gene to chromosome 3 at bands p26-p24 raises the possibility that it may be altered by certain nonrandom chromosomal abnormalities arising in human hematopoietic malignancies and solid tumors.

Human interleukin 5 (IL-5) plays an important role in proliferation and differentiation of human eosinophils. We report the isolation of cDNA clones from cDNA libraries of human eosinophils by using murine IL-5 receptor alpha chain cDNA as a probe. Analysis of the predicted amino acid sequence indicated that the human IL-5 receptor has approximately 70% amino acid sequence homology with the murine IL-5 receptor and retains features common to the cytokine receptor superfamily. One cDNA clone encodes a glycoprotein of 420 amino acids (Mr 47,670) with an NH2-terminal hydrophobic region (20 amino acids), a glycosylated extracellular domain (324 amino acids), a transmembrane domain (21 amino acids), and a cytoplasmic domain (55 amino acids). Another cDNA encodes only the extracellular domain of this receptor molecule. Other cDNA clones encode molecules having diversified cytoplasmic domains. COS7 cells transfected with the cDNA expressed a approximately 60-kD protein and bound IL-5 with a single class of affinity (Kd = 250-590 pM). The Kd values were similar to that observed in normal human eosinophils. In contrast to the murine 60-kD alpha chain, which binds IL-5 with low affinity (Kd = approximately 10 nM), the human alpha chain homologue can bind IL-5 with much higher affinity by itself. RNA blot analysis of human cells demonstrated two transcripts (approximately 5.3 and 1.4 kb). Both of them were expressed in normal human eosinophils and in erythroleukemic cell line TF-1, which responds to IL-5. The human IL-5 receptor characterized in this paper is essential for signal transduction, because expression of this molecule in murine IL-3-dependent cell line FDC-P1 allowed these cells to proliferate in response to IL-5.

The distribution of 125I-labelled recombinant mouse interferon-beta (rMuIFN-beta) in normal and glioma (203 glioma) bearing mice was studied by radioassay and macro-autoradiography at 15 and 30 min after a single intravenous injection. The level of rMuIFN-beta in the spleen was about 20-fold higher than in serum. Concentrations higher than the serum level was detected in the lung, liver and kidney. The concentration of rMuIFN-beta in the brain was 8% of the serum level and the concentration in the glioma 30 min after administration was about 10-fold higher than in normal mouse brain. Macro-autoradiographic study demonstrated a wide distribution range and selective uptake in glioma tissue. Furthermore, we found that mouse gliomas were sensitive to mouse IFN-beta. Our findings demonstrate that in the mouse glioma model, intravenously administered interferon reaches the tumour.

Murine interleukin-5 (IL-5) is known to play an essential role in Ig production of B cells and proliferation and differentiation of eosinophils. Here, we have isolated cDNA clones encoding a murine IL-5 receptor by expression screening of a library prepared from a murine IL-5 dependent early B cell line. A cDNA library was expressed in COS7 cells and screened by panning with the use of anti-IL-5 receptor monoclonal antibodies. The deduced amino acid sequence analysis demonstrates that the receptor is a glycoprotein of 415 amino acids (Mr 45,284), including an N-terminal hydrophobic region (17 amino acids), a glycosylated extracellular domain (322 amino acids), a single transmembrane segment (22 amino acids) and a cytoplasmic tail (54 amino acids). COS7 cells transfected with the cDNA expressed a 60 kd protein that bound IL-5 with a single class of affinity (KD = 2-10 nM). FDC-P1 cells transfected with the cDNA for murine IL-5 receptor showed the expression of IL-5 binding sites with both low (KD = 6 nM) and high affinity (KD = 30 pM) and acquired responsiveness to IL-5 for proliferation, although parental FDC-P1 cells did not show any detectable IL-5 binding. In addition, several cDNA clones encoding soluble forms of the IL-5 receptor were isolated. Northern blot analysis showed that two species of mRNAs (5.0 kb and 5.8 kb) were detected in cell lines that display binding sites for murine IL-5. Homology search for the amino acid sequence of the IL-5 receptor reveals that the IL-5 receptor contains a common motif of a cytokine receptor family that is recently identified.

Quasi-three-stage hardening is characterized with the existence of stage 0, and the temperature dependence of the length of stage I, which is opposite to that in the three-stage hardening in f.c.c. metals. The orientation dependence of these characteristics has been investigated for high purity iron single crystals. As the initial orientation of the specimen axis moves away from the [001]–[011] symmetry line, stage 0 becomes smaller and stage I becomes longer. As it approaches the [011]–[111] boundary, stage 0 becomes smaller and stage I becomes shorter. These results are interpreted using the mechanism of the quasi-three-stage hardening proposed by us recently and consideration of the slip plane dependence of the direction of the motion of screw dislocations in the primary and secondary slip systems.

mAb to murine IL-5R were prepared by means of fusion between mouse myeloma cells and spleen cells from a rat immunized with membrane-enriched fractions of IL-5-dependent early B cell line (T88-M). Two mAb (H7 and T21) were selected for their competitive inhibition of receptor binding by 35S-labeled IL-5 and of IL-5 biologic activities. The number of binding sites recognized by the mAb on different cell lines correlated with IL-5 responsiveness. Most surface IgM+ peritoneal B cells were H7+ and more than 70% were also Ly-1(CD5)dull+, and responded to IL-5 for polyclonal IgM production in a high frequency. A significant proportion of splenic B cells reacted with these mAb, although lower number (one-log less) than peritoneal B cells and a small proportion of H7dull+ splenic B cells seems to be Ly-1(CD5)dull+, 1 of 200 splenic B cells responded to IL-5 for IgM production. These results suggest that IL-5R+ B cells may consist of a subpopulation of B cells. Intriguingly, lymphoid populations of bone marrow cells were stained with H7 and T21, whereas myeloid populations were brightly stained with only T21. Finally, both H7 and T21 mAb specifically precipitated a protein of a Mr 60,000 from 125I-labeled cell lysates of IL-5R+ T88-M cells. The IL-5R with similar size (Mr 55,000 to 60,000) was precipitated from the cell lysates of peritoneal B cells. T21 mAb but not H7 mAb precipitated a protein of a Mr 110,000 from the cell lysates of bone marrow cells.

The angle-correlated energy differential cross-section for 9 Be(n,2n) reaction has been measured with the coincidence detection technique and a pencil-beam DT neutron source of FNS, JAEA. Neutron energy spectra of two emitted neutrons were separately obtained as azimuthal- and axial-angle differential value, which is called TDX. From the measured TDX, double-angle differential cross sections, ADDX, angular differential cross section, ADX, and total cross section, TOX, were deduced. In the TDX, a characteristic energy spectrum for beryllium was seen. The azimuthal ADDX unexpectedly showed a 180deg. symmetrical spectrum, not a flat one. From the result of TOX, JENDL-3.3 and ENDF/B-VI showed a little underestimation by around 10%.

N-{2-[2-(4-Phenylbutyl)benzofuran-4-yl]cyclopropylmethyl}acetamide 3a was synthesized as an orally bioavailable agonist at MT1 and MT2 melatonin receptors with significantly low vasoconstrictive activity.

A series of benzoxazole derivatives was synthesized and evaluated as melatoninergic ligands. The binding affinity of these compounds for human MT1 and MT2 receptors was determined using 2-[125I]-iodomelatonin as the radioligand. From this series of benzoxazole derivatives, compounds 14 and 17 were identified as melatonin receptor agonists.

A series of fluoren-9-yl ethyl amides ( 2 ) were synthesized and evaluated for human melatonin MT 1 and MT 2 receptor binding. N -[2-(2,7-dimethoxyfluoren-9-yl)ethyl]propanamide ( 2b ) was selected and evaluated in functional assays measuring intrinsic activity at the human MT 1 and MT 2 receptors and demonstrated full agonism at both receptors. The chronobiotic properties of 2b were demonstrated in both acute and chronic rat models where 2b produced an acute phase advance of 32 min at 1 mg/kg and chronically entrained free-running rats with a mean effective dose of 0.23 mg/kg. Compound 2b is significantly less efficacious than melatonin in constricting human coronary artery.

A novel series of benzoxazole derivatives was synthesized and evaluated as melatoninergic ligands. The binding affinity of these compounds for human MT(1) and MT(2) receptors was determined using 2-[(125)I]-iodomelatonin as the radioligand. The results of the SAR studies in this series led to the identification of compound 28, which exhibited better MT(1) and MT(2) receptor affinities than melatonin itself. This work also established the benzoxazole nucleus as a melatoninergic pharmacophore, which served as an isosteric replacement to the previously established alkoxyaryl core.

We have investigated a new bump forming process and developed a machine using solder paste. The ball bumps formed by the machine satisfied the planned EIAJ standards. The process is as follows. First, cavities are formed by superimposing a stencil onto a base plate. Secondly, they are filled with solder paste using a screening operation and a printed circuit board (PCB) is aligned face down on the stencil. Finally, they are heated together and solder paste is reflowed to be transferred onto the pads. The separable transfer jig is suitable for mass-production compared with block-type one, reducing the flux residue cleaning time, and realizing bump forming with a 0.3 mm pitch. The bump forming machine will be applied to the mass-production of chip scale packages (CSP) with a 0.8 mm pitch at the rate of 100,000 packages a month. We have also developed a new CSP with a unique structure as an application of the bump forming process.

This research work contributes to an active vision system for an gas pipe inspection robot moving inside of the pipe. The robot must be able to know what shape of the pipes where the robot is moving. The shapes of the pipe include straight, L or T. Also, when it is moving in the straight section, the robot must detect the relative angle with respect to its principal axis. The authors propose to use a laser spot array and TV camera for the vision sensor, which can find the three dimensional position of each spot on the surface of the pipe by means of triangulation. The shape of the pipe inside can be reconstructed by the information of the camera. A method is also presented to distinguish the shape whether it is straight or not.

[56038-00-7] C3H9KN2 (MW 112.24) InChI = 1S/C3H9N2.K/c4-2-1-3-5;/h4H,1-3,5H2;/q-1;+1 InChIKey = GXBBCEZQOPFZFX-UHFFFAOYSA-N (strong base1 used primarily for the isomerization of internal alkynes to terminal alkynes;2 can also be used to isomerize alkenes;3 also used to promote intramolecular transamidation reactions4) Alternate Name: KAPA. Solubility: highly sol (≥1.5 M) in excess 1,3-diaminopropane Preparative Methods: usually prepared as a solution in excess, dry 1,3-diaminopropane.5 The most common preparation involves the direct, quantitative reaction of Potassium Hydride with excess amine at 20–25 °C.6 Alternative preparations have been developed to avoid the handling and purification of KH. The reagent has been prepared by the reaction of Potassium Amide and 1,3-diaminopropane followed by evaporation of excess Ammonia in vacuo.7 The reagent has also been prepared by heating Potassium and 1,3-diaminopropane under sonication.8 A trace of iron(III) nitrate increases the rate of reagent formation, although it is not essential. Addition of Potassium tert-Butoxide to lithium 3-aminopropylamide (from Lithium and 1,3-diaminopropane) probably generates KAPA in situ via cation exchange.9 Handling, Storage, and Precautions: moisture sensitive. A solution of KAPA in 1,3-diaminopropane appears stable for at least 8 h at rt and possibly even for 2–3 days.2, 10 Use in a fume hood.

The application of a convergent benzannulation strategy in an efficient synthesis of (−)-ascochlorin is described.

Lnk is an SH2 domain-containing adaptor protein expressed preferentially in lymphocytes. To illuminate the importance of Lnk, we generated lnk(-/-) mice. Whereas T cell development was unaffected, pre-B and immature B cells accumulated in the spleens. In the bone marrow, B-lineage cells were proportionately increased, reflecting enhanced production of pro-B cells that resulted in part from hypersensitivity of precursors to SCF, the ligand for c-kit. Hence, Lnk ordinarily acts to regulate B cell production. Further characterization of lnk(-/-) mice also revealed that full-length Lnk is a 68 kDa protein containing a conserved proline-rich region and a PH domain. Lnk is a representative of a multigene adaptor protein family whose members act, by analogy with Lnk, to modulate intracellular signaling.

TRAF6, a member of the tumour necrosis factor receptor-associated factor family, was first identified as a transducer of CD40 and interleukin-1 receptor (IL-1R) signals based on the interaction of TRAF6 with the cytoplasmic tail of CD40 and with the IL-1R associated kinase in vitro. However, the functions of TRAF6 in vivo remain unidentified.We show that TRAF6-/- mice exhibit severe osteopetrosis and are defective in osteoclast formation. In vitro culture experiments revealed that osteoclast precursor cells derived from TRAF6-/- mice are unable to differentiate to functional osteoclasts in response to osteoclast differentiation factor (ODF). In bone marrow of TRAF6-/- mice, the number of sIgM+B220+ immature B cells is markedly reduced while the ratio of proB to preB cells is not affected. In contrast, development of thymocytes is not affected. Furthermore, TRAF6-/- mice are defective in lymph node organogenesis and IL-1 signalling in thymocytes.The results identify TRAF6 as an essential component of ODF signalling pathway, and also show that TRAF6 plays pivotal roles in immune and inflammatory systems in vivo.

The co-existence of multiple cerebral arteriovenous malformations (AVMs) and a spinal AVM is extremely rare. A 22-year-old man suddenly developed severe headache. Computed tomography (CT) scan showed intracerebral haemorrhage in the left occipital lobe. Cerebral angiography revealed eight AVMs; four were in the right frontal lobe and two each were in the right temporal and left occipital lobe, respectively. A huge high-flow spinal AVM was found incidentally. He had no other vascular lesions such as hereditary haemorrhagic telangiectasia. A left occipital craniotomy was performed and the ruptured left occipital AVMs were removed. Further therapeutic treatment was refused. To our knowledge, except for one autopsy case, this is the first reported patient with multiple cerebral AVMs with a spinal AVM. We discuss the characteristics of this case and review reported cases with cerebral and spinal AVMs.

Publisher Summary This chapter analyzes the pharmacologlcal interventions in the sleep process. Insomnia is the term used to describe difficulties in initiating sleep, maintaining sleep, or obtaining a restorative sleep. It is a symptom that can arise for a multitude of reasons and represents a significant public health problem. About 40% of the individuals suffering from insomnia attempt to self-medicate with over-the-counter agents or alcohol, indicating that a clear need still exists for accepted, effective medications. Because the likelihood of severe or chronic insomnia increases with age, the management of insomnia in the geriatric population is also a significant concern. The benzodiazepines (BZs) remain the mainstay of hypnotic therapy. The BZs produce their effects by acting at benzodiazepine receptors (BZRs) that are allosteric modulatory sites of the GABA A receptor. The chapter overviews current research aimed at improved pharmacological intervention in the sleep process and discusses the concepts related to GABA A benzodiazepine receptor ligands and melatonin receptor ligands. Aenosine receptor ligands are described and an overview of histamine receptor ligands is also presented.

Epirubicin and 5-FU were administered through an indwelling catheter inserted into the internal mammary artery and/or subclavian artery employing an implantable infusion port system for the treatment of unresectable advanced breast cancer and recurrent breast cancer. Intraarterial infusion chemotherapy proved to be an effective treatment modality for unresectable advanced breast cancer and recurrent breast cancer.

Stimulation of the T cell antigen receptor (TCR) activates a set of non-receptor protein tyrosine kinases that assist in delivering signals to the cell interior. Among the presumed substrates for these kinases, adaptor proteins, which juxtapose effector enzyme systems with the antigen receptor complex, figure prominently. Previous studies suggested that Lnk, a 38-kDa protein consisting of a single SH2 domain and a region containing potential tyrosine phosphorylation sites, might serve to join Grb2, phospholipase C-gamma1, and phosphatidylinositol 3-kinase to the TCR. To elucidate the physiological roles of Lnk in T cell signal transduction, we isolated the mouse Lnk cDNA, characterized the structure of the mouse Lnk gene, and generated transgenic mice that overproduce Lnk in thymocytes. Here we report that although Lnk becomes phosphorylated during T cell activation, it plays no limiting role in the TCR signaling process. Moreover, we have distinguished p38(Lnk) from the more prominent 36-kDa tyrosine phosphoproteins that appear in activated T cells. Together these studies suggest that Lnk participates in signaling from receptors other than antigen receptors in lymphocytes.

Publisher Summary Molecular characterization of a family of melatonin ( N -acetyl-5-methoxytryptamine) receptors has provided the foundation for new avenues of exploration. While the receptor proteins have been expressed in heterologous expression systems, data regarding precise localization of these receptors throughout the central nervous system (CNS) and periphery and how localization varies with species is limited. Melatonin first isolated from bovine pineal gland extracts is present in all mammalian species. Radio-iodination of melatonin produces [ 125 I]-iodomelatonin, a high affinity, high specific-activity radioligand suitable for discrete localization and pharmacological characterization of the melatonin binding sites. The target of melatonin's actions is thought to be the suprachiasmatic nucleus (SCN), a circadian clock in the suprachiasmatic nucleus of the hypothalamus, as an intact SCN, is necessary for melatonin to exert an effect on rodent circadian rhythms. The large number of melatonin receptor sequences available has prompted efforts to model receptor tertiary structure and to identify amino acid residues involved in ligand binding. All the models are based on the identification of key amino acids that can participate in hydrogen bonding to the methoxy group and to the amide of melatonin, both of which have been identified as critical interaction points for the molecule based upon structure–activity relationship (SAR) studies.

High-flow nasal canulae (HFNC) deliver high-flow humidified gas at up to 60 l/minute. There are two types of respiratory circuit to generate mix gas flow, Blender type (typeB) and Venturi type (typeV). The therapy is well established in the pediatric population and HFNC use has been described in the adult population. It has been reported that HFNC provide higher FIO2 compared with low-flow canulae, and also create mild positive pharyngeal airway pressure, but the effect on alveolar pressure is unknown. We aimed to investigate the effect of HFNC on alveolar pressure, by measuring intratracheal pressure in patients with a cricothyrotomy catheter (CTC). At the same time, we measured the actual gas flow rate (AGFR) by flowmeter and compared it with assumed flow.

In order to reduce toxic effects while attaining maximal therapeutic effects, epirubicin 10 mg/day, cyclophosphamide 100 mg/day and prednisolone 10 mg/day were administered through in indwelling catheter inserted into the internal mammary artery and/or subclavian artery for 3-4 weeks, employing the implantable port system for the treatment of unresectable breast cancer and recurrent cancer. Ten out of 11 patients (91%) with unresectable breast cancer showed a response (CR 3, PR 7, NC 1) to this modality of intra-arterial infusion chemotherapy. Seven out of 11 patients (64%) with recurrent cancer of the breast showed a response (CR 1, PR 6, NC 4). Intraarterial infusion chemotherapy for the unresectable advanced breast cancer and recurrent breast cancer proved to be an effective modality of treatment.

A new induction heating floating-zone refining (IHFZR) furnace was designed and constructed using ultrahigh vacuum technology for the ultrapurification of base metals. The ultrahigh vacuum attainable in this furnace is so good as 1x10 -7} Pa that a base metal bar can be zone-melted in both ultrahigh vacuum and higher-purity gas atmosphere containing less residual gases. The outline of this IHFZR furnace and the results of its application to the purification of high-purity iron, Fe-18%Cr alloy and Fe-50%Cr alloy are described. After only two zone-leveling passes in dry hydrogen, oxygen easily decreases in concentration from over 60 mass ppm to a few mass ppm ; on the other hand, carbon decreases in concentration not so easily as oxygen but gradually. As a result, ultrahigh-purity Fe-18%Cr alloy with the concentration of C+N+O+S of 12 mass ppm and ultrahigh-purity Fe-50%Cr alloy with the concentration of C+N+O+S of 10 mass ppm were obtained after only two zone-leveling passes and ten zone-leveling passes in dry hydrogen, respectively.

Fe-50mass%Cr was prepared in a cold crucible furnace with induction heating, then refined by floating-zone melting (FZM). The chemistries on the surface before and after FZM were compared by XPS measurement. C and O were observed on top surfaces both before and after as a hydrocarbon, carbonyl group and carboxyl group which are adsorbed chemical components. The other impurities were observed on the surface in both cases ; however, the number and level of impurities on the surface after FZM were much larger than those on the surface before FZM ; these adhered to the surface during sample preparation for XPS measurement. It is concluded that sample preparation introduces contamination which affects the detection limit of chemical analytical instruments. Sn was only observed on the top surface after FZM. It was segregated Sn which was contained in chromium as a starting material. It must be eliminated before starting. From XPS depth profiling results, it was concluded that 0.2 nm thickness of carbon such as hydrocarbon and organic components are adsorbed on the 1 nm thickness of oxide layer. Below the oxide layer, a lack of Cr was observed down to a depth of 6 nm.